Polymerase colony (polony) technology is a single-molecule amplification technology which allows the sequence of each individual molecule to be elucidated in a highly parallel manner. However, the throughput of polony technology is inversely proportional to the size of individual colonies, which ranges from tens to thousands of microns.
Methods for generating populations of clonal microspheres (i.e., beads bearing clonally amplified DNA) are known in the art (e.g., Dressman (2003) Proc. Natl. Acad. Sci. USA 100:8817; Brenner et al. (2000) Nat. Biotech. 18:630). However, these methods suffer from several drawbacks. In Dressman et al., beads are analyzed via fluorescence activated cell sorting (FACS), which is expensive to operate and suffers too low of a throughput (i.e., less than 70,000 events per second) to process hundreds of millions of beads. In Brenner et al., beads are manipulated to form a packed, planar array, such that the physical packing limits scattering of the beads.